Preliminary studies from our laboratories suggest two stages in the pathology of scleroderma (a) the cellular stage consisting of mononuclear cellular infiltrates and deposition of reticulin fibers, presumably Type III collagen, and (b) the fibrotic stage characterized mainly by the deposition of Type I collagen. The amounts of Type I and Type III collagens will be determined in the dermis and subcutaneous tissue from normal and scleroderma skin. Fibroblasts will be cultured from upper and lower levels of the skin to determine rate of collagen synthesis and the ratio of Type III to Type I collagens. Type I and Type III collagens will be obtained by limited pepsin digestion and salt fractionation. Following heat denaturation alpha chains will be separated by interrupted SDS-acrylamide gel electrophoresis. In order to rule out the presence of an altered form of collagen the alpha chains will be eluted, cleaved with CNBr and the peptides analyzed by SDS-15% acrylamide gel electrophoresis. Type I and Type III collagens will be further characterized by electron microscopy of segment long spacing (SLS) crystallites.